Researchers at Seoul National University Hospital (SNUH) and Toolgen, a local genome engineering company, said they succeeded in correcting a genetic mutation completely by delivering genetic materials to a mouse with Leber congenital amaurosis.
|Professor Kim Jung-hoon|
Leber congenital amaurosis is a common congenital retinal disease caused by mutations in genes related to visual function, such as RPE (retinal pigment epithelium) 65, CEP (congenital erythropoietic porphyria) 290.
Due to its hereditary retinal abnormality, which can cause congenital disorders, 10 to 18 percent of children with visual impairment suffer from the disease.
The researchers, led by Professor Kim Jung-hoon at SNUH, injected the adeno-associated virus vector carrying a CRISPR scissor and the normal RPE65 gene into the subretinal space of rd (retinal degeneration) 12 mice carrying the mutant RPE65 gene.
As a result, the healthy RPE65 protein synthesized into the retinal pigment epithelial cells of the rd 12 mice. In two retinal electrocardiograms, six weeks and seven months after treatment, the visual response of rd12 mice increased to 20 percent of normal mice, while also restoring the thickness of the retinal nerve cell layer.
“The study is significant as it completely corrected the genetic mutation,” the team said. “Although adeno-associated virus gene therapy has already been used to treat patients with Leber congenital amaurosis, it had limits as the mutant gene remained in the cell even after the injection.”
As a result, patients often became blind without receiving precise treatment, the team added.
In the new study, the team demonstrated that the mutant gene could be corrected entirely using the CRISPR scissors technology and has raised the possibility of more fundamental treatment of congenital retinal diseases, including Leber congenital amaurosis.
Professor Kim also said, “The study identified the possibility of fully correcting the genetic mutation that causes congenital retinal disease. The research will become the cornerstone for the development of future clinical trials.”
Science Advances published the results of the study.